| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Episodic knee arthralgia/flaring knee pain |
|
| E.1.1.1 | Medical condition in easily understood language |
| Knee pain or flare, a common condition in people who suffer from arthritic conditions. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10003239 |
| E.1.2 | Term | Arthralgia |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine if a 5 day treatment course of 1200 mg/day of ibuprofen in lipid formulation is non inferior to standard ibuprofen capsules (either 1200 mg /day or 2400 mg/day) for the pain subscale of the WOMAC in subjects suffering from episodic knee arthralgia/knee flare pain. |
|
| E.2.2 | Secondary objectives of the trial |
The key secondary objective is to determine if a 5 day treatment course of ibuprofen in lipid formulation (1200 mg/day) is superior to standard soft gel ibuprofen capsules (1200 mg/day or 2400 mg/day) for patient-reported gastrointestinal function-related quality of life using the Gastrointestinal Symptom Rating Scale (GSRS total score). This objective will assess the utility of the GSRS in assessment of gastrointestinal symptoms associated with ibuprofen exposure.
Other secondary objectives are to compare soft gel capsules of ibuprofen in lipid formulation (1200 mg/day) versus standard soft gel ibuprofen capsules (1200 mg/day and 2400 mg/day) in terms of changes in a number of other rating scores. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1: Male or female subjects between 18 and 70 years of age on the day of signing informed consent.
2: Noticeable pain in the index knee joint lasting >48 h at least 2 times during the previous 12 months either non treated or, requiring non-steroidal anti-inflammatory drugs (NSAIDs).
3: Subjects must rate knee pain as 5 or above based on pain specific NRS.
4: Willingness to abstain from the use of non-study pain medication (apart from paracetamol taken as advised by the Investigator, if required) from the time of onset of knee flare until receipt of study medication.
5: Willingness to abstain from use of NSAIDs (oral and topical other than those given as study treatment), other topical pain therapies (e.g., capsaicin), corticosteroids (systemic and intra articular), viscosupplementation, and other pharmacological pain treatments during the study.
6: Female subjects of childbearing potential must have a negative urine pregnancy test at baseline unless they are surgically sterile or have been post menopausal for ≥ 1 year (12 consecutive months without menses).
7: Female subjects of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least 90 days after the last dose of study treatment. Medically acceptable forms of birth control include, oral contraceptives, injectable or implantable methods, intrauterine devices, tubal ligation (if performed > 1 year before baseline ), or double barrier contraception.
8: Subjects must be able to understand and be willing to sign the informed consent prior to randomisation and agree to the study procedures.
|
|
| E.4 | Principal exclusion criteria |
1: History of serious illness or disease (e.g. progressive neurological signs, septic arthritis, fractures or significant injury or surgery to the knee(s) in the last 3 months.
2: Subjects who have undergone cholecystectomy.
3: BMI < 18 or >39 kg/m2 or a body weight <40 kg.
4: Diagnosis of systemic lupus erythematosus (SLE), mixed connective tissue disorders or autoimmune arthritis (e.g. rheumatoid arthritis, psoriatic arthritis) or receiving disease modifying anti-rheumatic drugs (DMARDs) or biologics.
5: Diagnosis of gout or use of allopurinol, febuxostat, colchicine.
6: Intra-articular corticosteroid to the index knee joint within 3 months prior to baseline visit or to any other joint within 4 weeks prior to baseline; hyaluronic acid intra-articular injection to the index knee joint within 6 months prior to baseline visit; systemic corticosteroids (oral, intramuscular or intravenous) within 4 weeks prior to baseline visit.
7: Radiotherapy for chronic articular pain within 3 months prior to baseline visit or planning the initiation of such therapy during the study.
8: Initiation of the use of medications for treating chronic pain (including anticonvulsants, tricyclic antidepressants, unselective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors, etc.) within 4 weeks prior to baseline visit or planning the initiation of any new anti-pain therapy or treatment during the study.
9: 9 Subjects taking selective serotonin reuptake inhibitors [SSRIs]
10: Any medication taken to alleviate pain prior to first dose of study medication other than paracetamol.
11: Clinically relevant history of hypersensitivity or allergy to study treatment or any other constituent of the drug: History of asthma, acute rhinitis, angioedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid, ibuprofen, or other NSAIDs, including COX-2 inhibitors.
12: Any medical condition other than pain due to OA that could interfere with study evaluations, e.g., anatomical deformities, fibromyalgia, chronic pain syndrome and neuropathy which would interfere with the assessment of pain.
13: Severe heart failure and congestive heart failure; history of clinically significant cardiovascular disease including, but not limited to, myocardial infarction, unstable angina, peripheral arterial disease, and stroke or transient ischemic attack; uncontrolled hypertension.
14: Active or previous history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding) or history of gastrointestinal bleeding or perforation related to previous NSAIDs therapy; history of gastrointestinal bleeding, history of inflammatory bowel disease.
15: Severe hepatic insufficiency.
16: Subjects with renal function GFR <60 mL/min/1.73 m2 based on the MDRD equation
17: Subjects with rare hereditary problems of fructose intolerance.
18: Any clinically significant condition that in the Investigator’s judgment may affect efficacy or safety assessments or may compromise the subject’s safety during study participation.
19: Participation in any interventional clinical study within 3 months prior to baseline visit.
20: History within the previous 2 years or current evidence of drug or alcohol abuse.
21: Pregnant or lactating women.
22: Any condition or circumstances which in the opinion of the Investigator may make a subject unlikely or unable to complete the study or comply with study procedures and requirements, or may pose a risk to the safety of the subject.
23: Subjects taking anticoagulant therpies |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is change from baseline after 5 days of treatment in the WOMAC pain score, for the full analysis set of subjects. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The primary endpoint will be evaluated after five days of treatment. |
|
| E.5.2 | Secondary end point(s) |
| If non-inferiority is observed for both group comparisons in the WOMAC pain score then formal statistical testing will be performed on the key secondary endpoint of the Gastrointestinal Symptom Rating Scale total score. This will be compared across the treatment groups using the same analysis methodology as for the primary analysis. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| This key secondary endpoint will be evaluated after 5 days of treatment. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of study is the Day 5 visit for those subjects whose flare up is either resolved or is under control sufficiently not to require further treatment. For those subjects reporting partial or uncontrolled flare (i.e. continuing pain, swelling and stiffness affecting mobility) which requires additional treatment (Day 6 to Day 10) their end of study will be a visit within 24 hours of their final dose. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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